TRANSCRIPTIONAL REGULATION OF OCI-5 GLYPICAN-3 - ELONGATION CONTROL OF CONFLUENCE-DEPENDENT INDUCTION/

OCI-5/Glypican 3, a member of the glypican family of proteoglycans, is the defective gene in the Simpson-Golabi-Behmel overgrowth syndrome. OCI-5 expression is developmentally regulated in the intestinal epithe lium, and the mechanism of its regulation was studied in the rat intes tinal epithelial cell line IEC-18. A large induction of OCI-5 transcri pt and protein was observed at high cell density, Among other glypican family members, kappa-glypican also exhibited a confluence-dependent induction in select cell types. Nuclear run-on analysis indicated that cell-density regulation of OCI-5 occurs at the level of transcription , The rat and mouse OCI-5 promoters were cloned and found to be highly conserved, located within CpG islands and contain regions of alternat ing purine and pyrimidine residues, No TATA-box or recognizable INR el ement was observed, Consensus binding sites for AP-2, SP-1, zeste and NF-1/CTF are conserved across human, mouse and rat promoters, 5' delet ion mapping of the rat promoter identified regions which enhance and r epress promoter activity, with no apparent confluence-dependence or ti ssue-specificity. Nuclear run-on analysis probing different regions of the gene suggests that elongation control plays a role in the inducti on of OCI-5 by confluence.